The first time it happened, Erin Bousquet was a high school freshman who had been diagnosed with strep throat, a common infection in her family. After three days on an antibiotic, she wasn’t getting better, so the 14-year-old was prescribed a second drug.
“It was quite scary,” Kristen recalled. “At first we thought she was joking.”
That bizarre episode, which occurred in September 2017, has been followed by 11 more, each lasting an average of 10 days. Between episodes, Erin’s behavior is normal.
For 2 1/2 years she and her parents, who live in Lincoln, Neb., consulted pediatric neurologists, a neurosurgeon, an obstetrician-gynecologist and other specialists in a largely fruitless search to identify the condition that drastically alters her personality and temporarily shuts down her life two or three times a year.
The diagnosis, made in March 2020, was an enormous relief. But it has required the Bousquets to cope with continued uncertainty because so little is known about Erin’s disorder.
“The hardest thing for me are the things I’ve missed out on,” said Erin, a 19-year-old sophomore at the University of Nebraska at Lincoln. They include a high school basketball championship, her 18th birthday, a family Christmas trip to Colorado and the start of her sophomore year of college. Erin slept through them all.
Screening for mono
Because her symptoms — disorientation and prolonged sleep — can be signs of a serious, even life-threatening, illness, the staff at the urgent care clinic where Erin had been treated for strep told her mother to take her to an emergency room. A test for infectious mononucleosis, a contagious virus common among adolescents and young adults that causes profound fatigue was negative and a quick neurological exam was normal. Erin was sent home.
A day later she saw the pediatrician who had treated her since birth. During the visit “she was slumping down in her chair” as if she was about to slide onto the exam room floor, Kristen recalled. “Her face was just empty.”
At that point Erin was sleeping almost around-the-clock, waking to eat, drink and go to the bathroom. She became angry when someone tried to rouse her or keep her awake. She spoke in a whisper, giving one-word answers to questions. Her behavior was childish, sometimes obnoxious and unfiltered — a stark contrast to her usual polite, even-keeled self.
The pediatrician “was stumped too,” recalled Kristen, who had started keeping a detailed log of her daughter’s symptoms, tests and treatments that would prove particularly useful later.
Erin’s doctor thought she might have been unknowingly drugged at a party or was using illegal drugs, possibilities her parents vehemently rejected. They noted that she was an honor student involved in multiple sports and other extracurricular activities who had a large group of friends.
After a negative drug test, the pediatrician suggested she might have a psychiatric problem and recommended medication for anxiety and depression. Kristen, skeptical that the problem was psychological, insisted instead on a referral to a pediatric neurologist. The neurologist admitted her to a hospital.
The psychiatrist who saw her during her three-day stay said he didn’t know what was wrong but believed the cause was probably physical, not psychological.
Neurologists initially suspected a form of autoimmune encephalitis, a serious inflammation of the brain requiring urgent treatment. The disease, also known as anti-NMDA receptor encephalitis, triggers odd behavior that mimics psychosis. Its causes include a benign ovarian tumor called a teratoma. But scans of Erin’s brain, abdomen and pelvis — along with an EEG that measures brain waves and tests of her blood and spinal fluid that were sent to the Mayo Clinic for analysis — turned up no signs of a tumor, infection or encephalitis.
Eight days after the odd behavior started it was as though “someone had flipped a switch,” her mother recalled. Erin was back to her old self but remembered little of what had happened. After a few nights of insomnia, her sleep pattern returned to normal.
An MRI scan of Erin’s brain performed while she was hospitalized had uncovered something unusual: a Chiari malformation, in which brain tissue extends into the spinal canal. A neurosurgeon thought the Chiari might have caused her symptoms, although they were hardly typical — a Chiari usually causes crushing headaches, neck pain and balance problems. He ordered a repeat scan in six months.
In May 2018 after a second scan showed no change, the surgeon said he doubted the Chiari had anything to do with the episode. No further treatment was necessary, he told the Bousquets, unless Erin developed new symptoms. The family, relieved that Erin did not have a serious brain malformation, moved on. Everyone hoped it was, as one doctor speculated, “a weird virus.”
But in June 2018, eight months after the initial episode, it happened again.
‘Blank stares from doctors’
This time Erin did not have strep. “She woke up fine,” but a few hours later her behavior changed abruptly and the sleep marathon began, Kristen recalled. Doctors, who were again concerned about encephalitis, admitted her and found no sign of the disease.
Erin was discharged three days later. “The fact that everything came back clean was great,” her mother said. “But at the same time you’re very scared … I got lots of blank stares from doctors. Nobody had ever seen anything like this.”
Over time a pattern seemed to emerge in the log Kristen was keeping. The episodes often started the day after Erin’s period began. During it she craved foods she rarely ate, including a specific sugary kids’ cereal, one brand of chicken nuggets, corn and ice cream sandwiches.
“She couldn’t follow the simplest instructions,” Kristen remembered. “I would tell her to take a shower and walk in and find her lying on the floor of the bathroom, her feet propped up on the toilet.”
Her personality change was unnerving and her uncharacteristic defiance sometimes embarrassing. She would “tell the hospital people to get out of her room,” her mother remembered. Once she tried to pull out her IVs.
The end of an episode was marked by a headache, euphoria, unusual talkativeness and a few nights of insomnia, during which Erin and her relieved mother caught up on what she had missed.
Each time Kristen struggled to tamp down her worries about the future. “My biggest fear was what if this happens again and she never comes out of it and she’s never Erin again?”
The apparent link to Erin’s menstrual cycle led to a new focus on a possible hormonal cause: premenstrual dysphoric disorder (PMDD), although its predominant symptoms include anxiety and depression, not altered behavior and marathon sleeping.
In summer 2018 Erin saw a fertility specialist who ordered blood tests, then prescribed injections to counter a sharp drop in two hormones that the obstetrician-gynecologist thought might be triggering the episodes. Another test showed mild insulin resistance, which can be a precursor to Type 2 diabetes. But six months of a diabetes drug along with hormone injections did not prevent episodes in March and July 2019.
“It seemed like it was mostly trial and error,” Kristen recalled of the treatments, which also included vitamins and changes to Erin’s diet.
Kristen said she and her husband, Greg, saw their role as advocates for their daughter, although they often felt unsure about what to do or where to turn. They routinely asked for referrals and when a doctor appeared disinterested, moved on.
“We were determined to find the right doctor and not to just settle for an easy answer or start random” drugs, Kristen said. The quest for a diagnosis, they believed, had to be balanced against their reluctance to disrupt Erin’s life “even more than the 20 missed days of the year already did.”
‘Not much else it could be’
In early 2020 the fertility specialist recommended that Erin consult Omaha neurologist Robert Sundell.
At the start of the March 18 appointment, Sundell said Kristen handed him a six-page, single-spaced chronology and launched into Erin’s story, starting at the beginning. “I told him everything that had happened,” she said.
Erin and her mother remember that Sundell, who is now on the staff of Methodist Health System, listened attentively, then excused himself.
He returned about 15 minutes later with news that floored them. He told them he believed Erin had Kleine-Levin Syndrome (KLS), a rare and little-known sleep disorder. Although 70 percent of cases involve adolescent boys, KLS is also known as “Sleeping Beauty Syndrome.”
Kristen said she remembers exclaiming, “Oh my gosh, that’s exactly what this is!”
Episodes typically last a few days to a few weeks and recur unpredictably. Childish or disinhibited behavior, irritability, increased appetite, food cravings and disorientation are common during episodes, as is amnesia.
Between episodes people with KLS usually function normally. The cause of the disorder is unknown and may be the result of genetic factors, an autoimmune response or a malfunction in parts of the brain that govern sleep and appetite.
No treatment has been found to be generally effective in preventing KLS, which can be misdiagnosed as depression or psychosis. The disorder often spontaneously resolves within about a decade of the initial episode, although it can recur later.
“With the retrospectoscope it was pretty clear,” Sundell said, using medical slang for hindsight. “There’s not much else this could be,” he said, adding that Erin “meets all the criteria.” Triggers include an infection, alcohol or the start of a period, he noted.
The neurologist said that while he knew of KLS, he had never seen a patient with it. In Erin’s case extensive testing had already ruled out a brain tumor, infection or other causes. “Most bad things get worse,” Sundell said, noting that Erin was healthy between episodes.
Sundell said he contacted other neurologists in Omaha, but none was familiar with the disorder. He also spoke with a sleep disorder specialist at the Mayo Clinic who offered to see Erin; the Bousquets declined. Erin now sees Sundell annually.
“Our approach has been watchful waiting and the hope that this goes away,” the neurologist said.
Kristen said that she has found contact with other families she met through the KLS Foundation to be largely reassuring. She is especially grateful to Sundell who has been unusually available and open to discussing possible therapies. The family hopes to participate in a Stanford University study of the disorder.
But each new episode, Kristen said, arouses “all the sad and scared feelings as I realize we have no control. When she is sick, our lives stop.”
Erin has tried to adjust to the fact that she never knows when she might be out of commission for nearly two weeks as she was in August, at the beginning of her sophomore year.
“It’s kind of hard to explain,” she said.